Effects of atorvastatin on the gene expressions of cyclooxygenase-2 and membrane-associated prostaglandin E2 synthase-1 in carotid atherosclerotic plaques of rabbits / 中华老年医学杂志

ABSTRACT

Objective To explore effects of atorvastatin on the expressions of cyclooxygenase-2(COX-2) and membrane-associated prostaglandin E2 synthase-1 (mPGES-1) in the carotid atherosclerotic plaques of rabbits.Methods Totally 33 male New Zealand white rabbits(≥ 36months of age ) were assigned into normal control group (n=8) and animal model group with carotid atherosclerotic stenosis (n =25).The rabbit models were randomly divided into non-intervention group,celecoxib treatment group (15 mg · kg-1 · d-1,twice daily) and atorvastatin treatment group (5 mg · kg-1 · d-1,once daily) (n=8 each).Four weeks after treatment,the mRNA and protein expressions of COX-2 and mPGES-1 in carotid plaques were determined by RT-PCR and Western blot,respectively.Results The mRNA expressions of COX-2 (0.97±0.09,0.44±0.05,0.60±0.04vs.0.23±0.04,F=66.77,P＜0.01) and mPGES-1 (0.92±0.07,0.41±0.04,0.61±0.03 vs.0.17±0.03,F=54.87,P＜0.01)in carotid atherosclerotic plaques were significantly higher in non intervention group,celecoxib treatment group and atorvastatin treatment group than in normal control group.The mRNA expressions of COX-2 and mPGES-1 were decreased in celecoxib treatment group and atorvastatin treatment group as compared with non-intervention group ( both P ＜ 0.01 ).The protein expressions of COX-2 (0.89±0.06,0.42±0.07,0.62±0.04 vs.0.18±0.05,F=61.75,P ＜0.01) and mPGES-1(0.91±0.05,0.44±0.05,0.63±0.05 vs.0.21±0.04,F=86.44,P＜0.01)in carotid atherosclerotic plaques in non-intervention group,celecoxib treatment group and atorvastatin treatment group were increased as compared with those in normal control group.The mRNA and protein expressions of COX-2 and mPGES-1 were decreased in celecoxib treatment group and atorvastatin treatment group as compared with non-intervention group(all P＜0.01 ).The expressions of COX-2 and mPGES-1 in carotid atherosclerotic plaques were reduced in celecoxib treatment group as compared with atorvastatin treatment group (P ＜ 0.01).Conclusions As COX-2 inhibitor celecoxib,atorvastatin may inhibit the expressions of COX-2 and mPGES-1,and interfere with the inflammatory response which plays key role in the pathological progress of carotid atherosclerotic plaques,and thus slow the progress of carotid atherosclerosis.